The cell walls of fungi evoke a powerful immune-stimulatory response. More than 50% of the cell walls of Candida albicans is composed of an inner layer of β-1,3/1,6-D-glucan covalently linked to a variety of cell surface mannoproteins [Klis, F. M. et al. FEMS Microbiol. Rev. 26, 239-259, 2002]. Preparations of these β-1,3/1,6-glucans act as immunostimulants [Lee, J. N. et al. Biosci. Biotechnol. Biochem. 65, 837-841, 2001; Sakurai, T. et al. J. Leukoc. Biol. 60, 118-124, 1996].
Specifically, β-1,6-D-glucan, more than β-1,3-D-glucan, has been shown to recruit and activate human neutrophils [Rubin-Bejerano I. et al., Cell Host Microbe. 2(1): 55-67, 2007]. The activation is mediated by endogenous anti-β-1,6-glucan antibodies, mostly of the IgG2 isotype [PCT/US09/42117], as well as C3 proteolytic fragments of the complement system [Rubin-Bejerano I. et al., Cell Host Microbe. 2(1): 55-67, 2007]. Therapeutic agents that include β-1,6-D-glucans can be conjugated to a targeting moiety (e.g., a cancer targeting antibody; see, e.g., PCT/US07/23307), as well as methods of using these conjugates as therapeutic agents, e.g., to treat various cancers.
Accordingly, compositions comprising β-1,6-D-glucan oligosaccharides of specific sizes can be useful for the preparation of therapeutic agents. In some embodiments, the oligosaccharides have been modified in a way that would allow conjugation to targeting moieties. Such chemically modified β-1,6-D-glucans have also been assayed for binding to the endogenous anti-β-1,6-D-glucan antibodies, thereby maintaining the desired function.